This project, entering its third year, explores the basic mechanisms responsible for the excess antibody production characteristic of the disease systemic lupus erythematosus. By studying both antigen-specific (anti-tetanus toxoid) and total immunoglobulin production both in vitro and in vivo, a few observations have been made. There is an abnormality in antibody production which relates to the SLE-B cells rather than to an abnormality of the regulatory SLE-T cells or SLE-monocytes. This B cell abnormality relates more to IgM than to IgG synthesis. Synthesis of antibody to tetanus toxoid following booster immunization is subnormal in about 1/3 of patients with SLE. This defect is again due to a SLE-B cell abnormality. In no case is an excess of anti-tet produced by patients with SLE showing that the overproduction of antibodies in SLE is restricted in specificity. This year these investigations will continue by the study of the regulation of anti-DNA synthesis in vitro; the study of the control of antibody synthesis to a primary immunogen; and the study of the role of circulating antilymphocyte antibodies in the control of antibody synthesis in SLE.